Primary hepatic lymphoma: a rare case.
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Female↗
Biomedical subjects
A Sood
Publications and source records attributed to A Sood.
Chronic hepatitis C--treatment results in northern India.
BACKGROUND: There have been major innovations in the treatment of chronic hepatitis C in the last decade. The course of the disease is variable and host, viral and environmental factors can influence the disease course and response to various treatment protocols. Data on the therapeutic response among north Indian patients with chronic hepatitis 'C' is limited. Therefore, we analysed our results of treatment among patients with chronic hepatitis C. MATERIAL & METHODS: A total of 55 patients with chronic hepatitis C were treated. Forty nine patients completed treatment with either interferon alpha 2b alone (n = 12) or combination of interferon alpha 2b and ribavarin (n = 37). All the patients were seropositive for anti HCV and, HCV RNA. All of them had elevated ALT and histological features of chronic hepatitis. Response to treatment was evaluated as end treatment response (ETR) i.e. HCV RNA not detected at end of treatment and sustained response (SR) i.e. HCV RNA not detected six months after completing the treatment. Adverse effects were also recorded. RESULTS: Overall, ETR was documented among in 69% of the patients and SR in 45% patients. Sustained response rate was higher with combination therapy as compared to interferon alone i.e. (51% vs 25%). Sustained response with induction dosing was 57%. Treatment had to be stopped in 3 patients due to major side effects like psychiatric disorders (2) and hypotension (1) and 3 patients were lost to follow up during the course of therapy. CONCLUSION: Sustained virological response with combination therapy is better than with interferon alone. Induction dosing improves the sustained virological response further. Major side effects with the antiviral drugs necessitating drug withdrawal is infrequent.
Adult↗
Hepatitis C--knowledge & practices among the family physicians.
BACKGROUND: Hepatitis C virus (HCV) is an important cause of end stage chronic liver disease worldwide. There is plethora of informations on hepatitis C virus in the recent hepatology related periodicals. However, family physicians to whom such patients initially present, should be aware of various aspects of hepatitis C virus infection. Therefore, the present study evaluated the information on hepatitis C virus known to practicing family physician in the state of Punjab. MATERIAL & METHODS: Nine hundred thirty six family physicians were randomly selected from 7 districts of Punjab and were mailed a questionnaire designed to test their knowledge on HCV, its transmission, clinical presentation, complications and treatment. In addition, questions were asked to assess commonly employed mode of therapy for short duration illnesses and the practice of reusing syringes/needles. All question had unequivocal answer. The questionnaire reply was anonymous. RESULTS: Only 28% (n = 262) doctors returned the questionnaire. The response to different sections of questionnaire was variable. Seventy six percent doctors (n = 176) were aware that HCV is parenterally transmitted. 18% (n = 41) doctors were still reusing needles and syringes. Fifty eight percent (n = 134) doctors considered hepatitis C as a common cause of acute viral hepatitis. Only 72% (n = 166) of doctors knew about the relevant tests for diagnosis of hepatitis C. CONCLUSIONS: Despite having knowledge about parenteral route of transmission of HCV infection, a sizeable proportion of family physicians in the Punjab state continues to reuse needles and syringes. Information on the virology, clinical presentation, diagnostic tests and management approaches were lacking among a substantial proportion of family physician. Therefore, awareness about HCV need to be increased among the practicing physicians.
Clinical Competence↗
The synthesis and antineoplastic activity of 2'-deoxy-nucleoside-cyanoboranes in murine and human culture cells.
The guanine, inosine, adenine and cytidine deoxyriboside cyanoboranes proved to be cytotoxic and possess in vivo antineoplastic activity against murine and human single cells and cultured cells derived from solid tumor lines. The agents preferentially inhibited DNA synthesis in Tmolt3 leukemic cells. The enzyme sites of drug inhibition of two active derivatives were DNA polymerase-alpha and de novo purine synthesis at the regulatory sites, PRPP amido transferase and IMP dehydrogenase. Moderate inhibition by the agents of TDP kinase and ribonucleoside reductase activities also occurred. Kinetic studies showed that IMP dehydrogenase activity was inhibited the earliest of all of the enzymes affected by the drugs. The d(ATP) pools were also reduced by drug treatment. DNA strand scission was evident after 24 hr incubation at 100 microM of drug. The 14C-cytidine-cyanoborane drug was rapidly taken up over 6 hr and most effective uptake was shown by rapidly dividing cells. The drug was bound to DNA, RNA and protein in Tmolt3 leukemic cells.
Animals↗
Antineoplastic activity of boron-containing thymidine nucleosides in Tmolt3 leukemic cells.
The sugar boronated thymidine nucleoside, 5' -0-[(triphenylphosphine-boryl) carbonyl]-3'-0-acetyl thymidine 1, and the boron-modified nucleoside phosphotriester, 5'-(diethylphosphite- cyanoborane)-3'-acetylthymidine 2, were successfully synthesized. Both compounds demonstrated differential activity when tested against eight cell lines, with significant cytotoxic activity against the growth of human Tmolt3 leukemia, colon adenocarcinoma, HeLa S3 uterine carcinoma, and osteosarcoma cells. In in vivo studies these agents were found to be active against the growth of Ehrlich ascites carcinoma at 8 mg/kg/day I.P. and to be marginally active against the growth of L1210 and Lewis lung cancers in mice. The mode of action of these thymidine derivatives in Tmolt3 cells was the inhibition of DNA and protein synthesis. Compound 2 was highly effective in inhibiting DNA polymerase alpha and m-RNA, r-RNA and t-RNA polymerase activities. Both compounds inhibited ribonucleoside reductase activity. The de novo purine pathway appeared to be the major site of inhibition of the agents, with IMP dehydrogenase, PRPP amido transferase, and dihydrofolate reductase activities being significantly inhibited. In the pyrimidine pathway, carbamyl phosphate synthetase and aspartate transcarbamylase activities were inhibited by 1. As expected, d[NTP] levels were significantly reduced by treatment with the agents. DNA strand scission was evident after incubating Tmolt3 cells for 24 hr with the agents.
Animals↗
Synthesis, antineoplastic activity and biodistribution of boron analogues of amino acids and related compounds.
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Amino Acids↗
The cytotoxicity of 3'-aminocyanoborane-2', 3'-dideoxypyrimidines in murine and human tissue cultured cell lines.
3'-Aminocyanoborane-2', 3'-dideoxythymidine (VIIa) and 3'-aminocyanoborane-2', 3'-dideoxyuridine (VIIIb) were successfully synthesized. The thymidine derivative (VIIIa) was shown to be a potent cytotoxic agent in murine and selected human suspended and solid tumor cell lines. Compound VIIIa inhibited L-1210 leukemia DNA and RNA synthesis with the protein synthesis requiring a higher concentration of drug for inhibition within 60 min. The purine pathway appeared to be the major target of Compound VIIIa with inhibition of IMP dehydrogenase and dihydrofolate reductase activities. The compound affected metabolic enzyme activities in the pyrimidine pathway as well as the nucleoside kinase activities. The DNA molecule did not appear to be target of the 3'-aminocyanoborane-2', 3'-dideoxythymidine (VIIIa), in that there was no change in ct-DNA viscosity, thermal denaturation or absorption of nucleosides of DNA nor was there any L-1210 DNA strand scission or inhibition of L-1210 DNA topoisomerase II activity when compound VIIIa was incubated at 100 microM.
Animals↗
Cytotoxicity of ribo-and arabinoside boron nucleosides in tissue culture cells.
Ribose and arabinoside boron nucleoside derivatives were shown to be potent cytotoxic agents in murine and human suspended and solid tumor cell lines. The arabinoside derivative inhibited DNA and RNA synthesis with the protein synthesis requiring a higher concentration of drug for inhibition within 60 min. The purine pathway appeared to be the major target of the arabinoside 1 with inhibition of PRPP amido transferase and IMP dehydrogenase activities. Blockage of this pathway afforded reductions of deoxyadenosine and deoxyguanosine nucleotide pools. The DNA template did not appear to be target of the arabinoside 1, in that there was no change in DNA viscosity, thermal denaturation or absorption of nucleosides of DNA. However, compound 1 when incubated with L-1210 cells for 24 hr. showed a slight shift of the DNA in the gradient and moderate inhibition of ct-DNA topoisomerase II was demonstrated by 1 in vitro.
Animals↗
Radionuclide (MUGA) studies of left ventricular functional abnormalities in asymptomatic patients with sickle cell anemia.
Radionuclide ventriculography was performed on 10 normal subjects and 39 patients with sickle cell anemia (10 homozygous and 29 heterozygous sicklers) at rest and after exercise. Their left ventricular (LV) function was assessed in both these situations. The results were then compared within the subgroups. The reduction in ejection fraction (EF) response (47.5 +/- 7 at rest and 46.4 +/- 8 at exercise in homozygous patients, and 52.4 +/- 8 at rest and 54.3 +/- 8 at exercise in heterozygous patients) was significant in both the homozygous and the heterozygous groups but more so in the former group. The diastolic filling was also significantly impaired in the homozygous group (PER 2.64 +/- 0.74, PFR 2.13 +/- 0.42 and PFR/HR 0.014 +/- 0.001). The study statistically demonstrates, that LV filling patterns are altered in the sickle cell patients, even in the absence of clinical symptoms relating to LV dysfunction. This fact may prove to be a marker of sickle cell heart disease. Frequent and significant sickling is probably the cause of more pronounced LV functional abnormalities in homozygous sicklers.
Adult↗
Boron substituted deoxyribonucleosides as cytotoxic agents.
Base substituted boronated nucleosides and phosphate modified nucleotides were examined for their cytotoxic activity in both murine and human tissue cultured cancer cells. These derivatives demonstrated better activity against the growth of single cell suspensions than solid cell tumor cell growth. A detailed mode of action study showed that 2'deoxyriboadenosine-N7-cyanoborane 6 suppressed Tmolt3 DNA synthesis preferentially with the major target of the agent being the purine de novo pathway. The activities of one of the regulatory enzymes of the pathway were reduced by the agents, i.e. PRPP-amido transferase. Other sites in the cell which were moderately affected by the agent were nucleoside kinase activities. DNA polymerase alpha and dihydrofolate reductase activities. The DNA molecule itself did not appear to be a target of the compound.
Animals↗
The cytotoxicity of adenosine 5'-[N,N-di-(gamma-o-carboranyl)propyl] phosphorodiamidate in human Tmolt3 leukemic cells.
Adenosine 5'[N,N-di-(gamma-o-carboranyl)propyl] phosphorodiamidate 1 was successfully synthesized and characterized. The compound demonstrated potent in vivo antineoplastic activity and in vitro cytotoxicity in murine and human leukemia and uterine carcinoma tumor cell lines. In human T cell leukemia DNA preferentially was inhibited with key enzymes in the purine pathway being effectively inhibited by the agent. Marginal inhibition of the activities DNA polymerase a, carbamyl phosphate synthetase, nucleoside kinases, and thymidylate synthetase was observed. Tmolt3 DNA strand scission was observed after 24 hr. incubation with compound I at 100 microM.
Adenosine↗
The influence of the p53 codon 72 polymorphism on ovarian carcinogenesis and prognosis.
The frequency of dysfunction of the p53 tumor suppressor gene in cancer has made the concept of gene replacement therapy with wild-type p53 an attractive strategy. Codon 72 of the p53 gene is highly polymorphic with a reported arginine/proline allelotype frequency of 0.65/0.35 for Caucasians and a reversal of this ratio in African-Americans. Ovarian cancer is more common and less aggressive in Caucasians. The arginine and proline alleles have different biochemical properties. Thus, we have hypothesized that these alleles may also have different biologic properties that could make one superior to the other for gene replacement therapy. To test this hypothesis in vivo, we investigated the prevalence of each allelotype in a population of 190 Midwestern American women with ovarian cancer and 52 healthy controls without a family history of cancer. We have found that: (1) the heterozygous arginine/proline allelotype is more common in probands with borderline cancers than in probands with invasive cancers (P = .0001) or healthy controls (P = .005); (2) despite a survival advantage (P = .006), probands homozygous for the arginine allele developed ovarian cancer at an earlier age (P = .01); (3) the frequency of tumor p53 mutations was independent of the germline p53 allelotype, but (4) when a loss of heterozygosity occurred in probands with invasive disease, the proline allele was lost preferentially (P = .002), and (5) any tumor which retained a proline allele was more prone to mutation (P = .04) than a tumor without a proline allele. Our results suggest that variation in the p53 codon 72 allelotype is an example of an intermediate risk polymorphism which interacts with epigenetic factors to play a role in ovarian carcinogenesis and may differentially influence cellular DNA repair and apoptotic pathways. These findings may have important ramifications in the choice of wild-type p53 genotype for gene replacement therapy of ovarian cancer.
Adult↗
Synthesis and antitumor activity of boronated dipeptides containing aromatic amino acids.
N-[(Trimethylamine-boryl-carbonyl]-L-tryptophan methyl ester and N[(trimethylamine-boryl)-carbonyl]-L-histidine methyl ester were obtained by synthesis using triphenyl-phosphine/carbon tetrachloride or dicyclohexyl-carbodiimide as coupling agents, respectively. Both agents reduced L1210 lymphoid leukemia DNA, RNA, and protein syntheses with the largest reductions occurring in DNA synthesis. Reductions in DNA synthesis appear to be mediated by inhibition of key enzyme activities (i.e., DNA polymerase a, IMP dehydrogenase, and PRPP amido transferase). These agents had little effect on in vitro L1210 DNA topoisomerase II activity at 100 microM but were able to cause synergistic increases in protein-linked DNA breaks when combined with etoposide (VP16). It was shown that these agents significantly reduced protein kinase C mediated phosphorylation of human topoisomerase II in vitro. Thus, inhibition of topoisomerase II phosphorylation may be a mechanism by which these agents and VP-16 are synergistic in causing protein-linked DNA breaks.
Animals↗
Relevance and importance of universal salt iodization in India.
It is well known that iodine and thyroid hormone are essential for normal development of the human brain and body. Lack of iodine in the diet leads to 'visible' and 'invisible' spectrum of iodine deficiency disorders. The prevalence of iodine deficiency can be assessed by estimating the total goitre rate in the population. A large section of the Indian population suffers from iodine deficiency disorders. These are easily preventable as was shown more than 40 years ago in the study conducted in Kangra Valley. Salt is the best medium of iodine supplementation in India. The potential risks of iodine supplementation, including the risk of iodine-induced thyrotoxicosis, are discussed. Finally, we attempt to formulate policy guidelines on iodine supplementation on the basis of presumed risk:benefit ratio for carrying out an iodine supplementation programme. Taking into consideration medical, social, economic and political aspects of universal salt iodization, the benefits far outweigh the potential low risk due to iodine excess in a small segment of the population.
Deficiency Diseases↗
Substituted carboranes and polyhedral hydroborate salts as anti-neoplastics.
Substituted carboranes and polyhedral hydroborate salts were observed to be potent anti-neoplastic/cytotoxic agents inhibiting the growth of mouse and human leukemias, human uterine, colon adenocarcinoma, lung bronchogenic and gliomas. Amino-o-carborane-hydrochloride 7, one of the more potent compounds, preferentially inhibited Tmolt3 DNA synthesis. The target of the agent appears to be de novo purine synthesis with significant inhibition of the activities of both regulatory enzymes, PRPP-amido transferase and inosine monophosphate dehydrogenase as well as dihydrofolate reductase. The agent also inhibited nucleoside kinase activities leading to reductions in deoxyribonucleotide pools. The DNA molecule itself was not a target of the agent.
Adenocarcinoma↗
A case of enteric fever with unusual manifestations.
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Adult↗